This PEN application aims to establish a highly collaborative and multidisciplinary Program of Excellence in Nanotechnology by integrating the bioengineering expertise of Georgia Tech (Atlanta, GA) and the cardiology strengths of Emory University School of Medicine (Atlanta, GA). The broad and long-term goal of this PEN is to develop nanotechnology and biomolecular engineering tools and methodologies for the detection and molecular analysis of atherosclerotic plaque formation, which has a compelling medical need. Cardiovascular disease remains the leading cause of death in the United States: One out of every four Americans has cardiovascular disease, and every 30 seconds one person dies from this disease. Although significant advances have been made in the management and treatment of this disease, there is still a lack of understanding of the fundamental biology and pathophysiology of atherosclerosis, especially the molecular mechanisms responsible for plaque formation. As a result, early detection of atherosclerotic plaque is difficult, leading to a high rate of morbidity and mortality. We propose to develop advanced nanotechnologies for molecular analysis of plaque formation and sensitive detection of plaques. Specifically: (1) we will develop the molecule beacon based technology for mRNA expression and localization in living cells in response to shear stress;(2) we will develop quantum dot (Qd) based probes for studying protein interactions in cells;(3) the QD probes will be further developed for in vivo detection and analysis of plaques;(4) we will develop magnetic nanoparticle probes for in vivo plaque detection;(5) we will carry out a pilot project to develop LDL and chymase based contrast agent for in vivo plaque detection;(6) as a second pilot project we will develop activatable probes for detecting oxidative stress in living cells. Underlying this PEN is a strong track record of the senior investigators who have worked together successfully in attracting joint research grants. In addition, the Department of Biomedical Engineering, which was jointly established in 1997 by Georgia Tech and Emory University School of Medicine, has presented unique opportunity for research collaboration and skill training by bring bioengineering, nanotechnologies and discoveries into medicine and vice versa. If funded, this Program of Excellence in Nanotechnology will be housed on the Emory Campus and with a truly outstanding environment for collaborative and translational cardiovascular research and training. In additional to basic knowledge on cardiology, this PEN is expected to yield methodologies that can direct impact on clinical practice of early detection, diagnosis and treatment of atherosclerosis.